Is RECQL4 p.Pro916= (c.2748G>A) pathogenic?

RECQL4 p.Pro916= (c.2748G>A) is classified Likely benign in RECQL4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). Ultra-rare (popmax 0.0204%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with RECQL4 p.Pro916= (c.2748G>A)?

RECQL4 p.Pro916= (c.2748G>A) is associated with hereditary neoplastic syndrome, Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Pro916= (c.2748G>A) in the general population?

RECQL4 p.Pro916= (c.2748G>A) is ultra-rare (popmax 0.0204%, amr) (gnomAD).

RECQL4 p.Pro916=

c.2748G>A · rs370679924 · VCV696657

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0204%, amr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13	GERP -3.5
Overall
CADD	0.039	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0204% Admixed American · 12/58,694 alleles

Filtering AF 0.0118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00917%

Overall 0.00574% 92/1,603,972 alleles · ultra-rare exomes 71/1,451,720 · genomes 21/152,252 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0204%	4,891
African / African-American	0.0187%	5,345
European (non-Finnish)	0.00519%	19,275
Remaining individualsnot grpmax-eligible	0.00322%	31,054
East Asian	0.00225%	44,488
Finnishnot grpmax-eligible	0.00161%	62,036
South Asian	0.00111%	89,778

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: RECQL4
Protein: p.Pro916=
Coding: c.2748G>A
MANE Select: NM_004260
dbSNP: rs370679924
Type: single nucleotide variant
Location: chr8:144512854 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 916: a UniProt-annotated variant site (in rts2)

Full RECQL4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Baller-Gerold syndrome

Similar variants

RECQL4 p.Pro916Leu Uncertain significance ★★ ⚠ same residue
RECQL4 p.Pro916Gln Uncertain significance ★ ⚠ same residue
RECQL4 p.Pro916Ser Uncertain significance ★ ⚠ same residue
RECQL4 p.Pro916Thr Uncertain significance ★ ⚠ same residue
RECQL4 c.1132-1G>A Likely pathogenic ★★ same condition
RECQL4 c.1259-1G>A Pathogenic/Likely pathogenic ★★ same condition
RECQL4 c.1391-1G>A Pathogenic ★★ same condition
RECQL4 c.1704+1G>A Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/recql4-p-pro916 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown